A 60-year-old woman with secondary chronic cluster headache had increased serum ferritin and serum transferrin saturation and was homozygous for the C282Y mutation in the HFE gene, which is indicative of hereditary haemochromatosis. Treatment with venesection that normalized her iron stores led to a radical improvement of her headache complaints that had been daily for several years. Later, the headache returned to some degree in spite of normal serum ferritin levels. Her cousin, a 33-year-old man who had had episodic cluster headache for several years, also had increased transferrin saturation and was compound heterozygous for two mutations, a genotype known to be associated with a slightly increased frequency of haemochromatosis. This is the first report of a headache disorder in a patient with hereditary haemochromatosis. The coexistence of the two disorders may be a mere coincidence, but the temporary improvement of headache from depletion of iron stores may indicate a causal relation, possibly mediated by iron deposits in pain-modulating centres in the brainstem.